ABSTRACT One of the most common congenital birth defects, craniofacial anomalies profoundly impact both form and function within the oral cavity. Sustained dysmorphology and dysfunction impairs feeding, compromises systemic health, and, ultimately, requires functional adaptation for survival. Chewing, the initial step in the digestive process, is a ubiquitous yet intricately coordinated function that precisely integrates craniofacial musculature and neural crest cell-derived components of the cranial system, specifically the jaws and teeth. While changes such as tooth wear are known to occur over the course of a lifetime, less is known regarding the role of genetically determined dental morphology on chewing kinematics and masticatory adaptation. Our lab has developed a unique tool that allows us to specifically investigate the relationship between dental morphology and masticatory function. This neural crest cell-specific, Evc2 conditional knockout (?Evc2 cKO?) mouse model presents with an abnormal dental and craniofacial phenotype similar to human Ellis-van Creveld syndrome patients. By specifically disrupting gene function in non-muscle cells, we seek to unravel the relationship between genetically determined dental morphology and masticatory adaptive capacity and have the potential to improve unbiased evaluation of oral performance in craniofacial anomaly patients. The overall hypothesis of this proposal is that inherent molar abnormalities result in subphysiologic masticatory patterns and muscle phenotypes that thereby impair masticatory adaptation. This project proposes the following aims: 1) characterization of the dentoskeletal morphology of our lab?s unique Evc2 cKO mouse model, 2) analysis of the functional and masticatory variation resulting from genetically determined (i.e. Evc2 deletion) craniofacial modification, and 3) evaluation of the physiological and functional adaptive capacity of Evc2 cKO mice. The proposed in vivo experiments will make use of both established and novel methodologies while evaluating dental morphology and adaptive capacity in an animal model of human disease. The outcomes of these experiments will not only enhance our knowledge of the relationship between form, function, and adaptation in the craniofacial region, but will also determine the clinical utility of our lab?s unique mouse model. Furthermore, elucidating this relationship while simultaneously developing new technique applications will be a key strategy for assessing other animal models of human disease and ultimately affect how we manage craniofacial anomaly patients.